The leukotriene B4 receptor functions as a novel type of coreceptor mediating entry of primary HIV-1 isolates into CD4-positive cells
(1998) In Proceedings of the National Academy of Sciences 95(16). p.9530-9534- Abstract
- The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive... (More)
- The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive cells expressing either CCR5 or CXCR4. Seven of the isolates used CMKRL1 for viral entry; they were mainly of the syncytium-inducing phenotype and also used CXCR4. Entry efficiency was higher with CMKRL1 than with CXCR4 for more than half of these isolates. Three of the ten isolates did not use CMKRL1; instead, entry was mediated by both CCR5 and CXCR4. The experiments thus indicate that CMKRL1 functions as a coreceptor for the entry of HIV-1 into CD4-positive cells. In the course of this study, leukotriene B4 was shown to be the natural ligand for this receptor (now designated BLTR), which therefore represents a novel type of HIV-1 coreceptor along with the previously identified chemokine receptors. BLTR belongs to the same general chemoattractant receptor family as the chemokine receptors but is structurally more distant from them than are any of the previously described HIV-1 coreceptors. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1113448
- author
- Owman, Christer LU ; Garzino-Demo, A ; Cocchi, F ; Popovic, M ; Sabirsh, Alan LU and Gallo, R C
- organization
- publishing date
- 1998
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 95
- issue
- 16
- pages
- 9530 - 9534
- publisher
- National Academy of Sciences
- external identifiers
-
- pmid:9689114
- scopus:0032482753
- ISSN
- 1091-6490
- language
- English
- LU publication?
- yes
- id
- 26f11a82-7c8e-4243-a0c8-550f738d67f2 (old id 1113448)
- alternative location
- http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21372
- date added to LUP
- 2016-04-01 12:20:44
- date last changed
- 2022-01-27 02:18:55
@article{26f11a82-7c8e-4243-a0c8-550f738d67f2, abstract = {{The recently cloned human chemoattractant receptor-like (CMKRL)1, which is expressed in vivo in CD4-positive immune cells, has structural homology with the two chemokine receptors C-C chemokine receptor (CCR)5 and C-X-C chemokine receptor (CXCR)4, which serve as the major coreceptors necessary for fusion of the HIV-1 envelope with target cells. In view of the structural similarity, CMKRL1 was tested for its possible function as another HIV-1 coreceptor after stable expression in murine fibroblasts bearing the human CD4 receptor. The cells were infected with 10 primary clinical isolates of HIV-1, and entry was monitored by semiquantitative PCR of viral DNA. The efficiency of the entry was compared with the entry taking place in CD4-positive cells expressing either CCR5 or CXCR4. Seven of the isolates used CMKRL1 for viral entry; they were mainly of the syncytium-inducing phenotype and also used CXCR4. Entry efficiency was higher with CMKRL1 than with CXCR4 for more than half of these isolates. Three of the ten isolates did not use CMKRL1; instead, entry was mediated by both CCR5 and CXCR4. The experiments thus indicate that CMKRL1 functions as a coreceptor for the entry of HIV-1 into CD4-positive cells. In the course of this study, leukotriene B4 was shown to be the natural ligand for this receptor (now designated BLTR), which therefore represents a novel type of HIV-1 coreceptor along with the previously identified chemokine receptors. BLTR belongs to the same general chemoattractant receptor family as the chemokine receptors but is structurally more distant from them than are any of the previously described HIV-1 coreceptors.}}, author = {{Owman, Christer and Garzino-Demo, A and Cocchi, F and Popovic, M and Sabirsh, Alan and Gallo, R C}}, issn = {{1091-6490}}, language = {{eng}}, number = {{16}}, pages = {{9530--9534}}, publisher = {{National Academy of Sciences}}, series = {{Proceedings of the National Academy of Sciences}}, title = {{The leukotriene B4 receptor functions as a novel type of coreceptor mediating entry of primary HIV-1 isolates into CD4-positive cells}}, url = {{http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21372}}, volume = {{95}}, year = {{1998}}, }